tbuckley/cabot-search huggingface dataset:
Trends and outcomes of systemic therapy in hormone receptor-positive early-stage male breast cancer: A propensity score analysis.
Authors: Liuwen Yu, Bangwei Zeng, Minyan Chen, Meng Huang, Wenhui Guo, Lili Chen, Yuxiang Lin, Jing Li, Yan Li, Fangmeng Fu, Lisa K. Jacobs, Chuan Wang
Journal: Journal of Clinical Oncology (2023)

557 Background: Male breast cancer (MBC) is a rare disease. Research on trends and survival outcomes in systemic treatment for MBC is limited. This study aims to describe trends and survival outcomes of different systemic treatments in hormone receptor-positive (HR+) early MBC and to assess the factors related to treatment selection. Methods: We identified stage I-III HR+ invasive MBC patients who have undergone surgery and systemic therapy diagnosed during 2004-2014 from the National Cancer Database (NCDB). Treatment groups include: endocrine therapy (ET), chemotherapy (ET), combination therapy (ET+CT), and None. Using Cochran-Armitage trend tests to describe the temporal trends of different treatments. Performing propensity score models to evaluate overall survival. Conducting a logistic regression to analyze factors associated with ET+CT. Results: Among 6217 patients included (median follow-up 50.1months), 1290 (20.7%) patients received no systemic therapy (None), 705 (11.3%) patients only received CT, 2358 (37.9%) patients only received ET, and 1864 (30.0%) patients received ET+CT. From 2004 to 2013, there was a significant increase in the use of ET ( P(trend) &lt; .001), which was accompanied by a decrease in CT and no treatment (all P(trend) &lt; .001). And the use of ET+CT showed no significant change. After using overlap weighting (OW) to control confounders, multivariable cox regression analysis showed that ET+CT was associated with improved survival compared with ET (hazard ratio [HR], 0.46; P&lt; .001). Sensitivity analyses (including the inverse probability of treatment weighting (IPTW) (HR,0.49; P &lt; .001), IPTW with stabilized weight (HR,0.49; P&lt; .001), propensity score matching (PSM) (HR,0.51; P &lt; .001), PS regression adjustment (HR,0.47; P &lt; .001), and PS stratification (HR 0.44; P &lt; .001)) and exploratory subgroup analyses (except for well-differentiated, stage I, and breast conservation + radiotherapy subgroups) indicated similar outcome. Factors associated with receiving ET+CT include younger age, private insurance, Charlson Comorbidity Index was 0, poorer differentiation, higher stage, mastectomy and radiotherapy, estrogen receptor-positive and progesterone receptor-negative, and HER2-positive. Conclusions: ET+CT was associated with improved survival compared with ET in HR+ early MBC patients, except for some low-risk subgroups.
Clinicopathological characteristics and outcome of very young breast cancer patients at a referral center in Iran.
Authors: Mona Malekzadeh Moghani, Atieh Sadat Hashemi, Narges Bazgir
Journal: Journal of Clinical Oncology (2023)

e12568 Background: Although breast cancer (BC) is the most common type of cancer in women worldwide, in women younger than 35 years old is uncommon and only accounts for 2% of breast cancer diagnosed in western countries. However, there is insufficient data on breast cancer in women younger than 35 years old in Iran. The aim of this study was to assess clinicopathological parameters in these very young breast cancer patients. Methods: In this retrospective cohort study, we have collected the demographic, clinical and histopathological data of women younger than 35 years diagnosed with BC who presented to our tertiary center from 2011 to 2017. Patients were followed at least for four years and the diseases-free survival (DFS) and overall survival (OS) were assessed. Chi-square and multivariate regression tests were conducted to assess the association of mentioned variables. A P-value less than 0.05 was considered to be statistically significant. Results: A total of 334 women with Breast Cancer younger than 35 years old were included in this study, of which 219 patients were between 31 to 35. The most common histopathologic type was hormone receptor positive, HER2 negative 41.6 %. HER2 positive (regardless of hormone receptor status) and triple negative were 30.1% and 24.6% of cases respectively. Grade1 was reported in 5% of cases, grade 2 and 3 were 50.9 % and 43.6% respectively. 16.9% of patients were presented in stage I, 44.4% stage II, 30.5% stage III and 8.2% had de novo metastatic disease. Of 68 patients who received neoadjuvant chemotherapy, 29.4% had complete pathological response. Sixty five percent of 199 patients with hormone positive had received Luteinizing hormone-releasing hormone (LHRH) agonist, this type of treatment significantly improved 4-year OS regardless of HER2 expression. Mean follow up was 71.5±26.6 months, 4-year DFS and OS were 66% and 80% respectively. Four-year overall survival was analyzed by stage, it was 100% for stage I, 89% stage II, 79% stage III, and 11% stage IV. The four-year OS corresponding to the subtypes was as follows; HR+/HER2- (89.5%), HR+/HER2+ (76.9%), HR-/HER2+ (73.3%) and TNBC (75.4%). Conclusions: Breast cancer occurring in very young women constituted 9.5% of all breast cancer cases treated at Shohada Hospital, Iran, and this high rate shows a significant correlation with unpublished data by Health ministry in 2016-2017. This high percentage is an alarm not only in breast clinics but also in early detection of breast cancer. In according to other published data, clinicopathological subtypes in our center was similar to other papers. The associations of subtypes with stage and grade, were significant.
The impact of SARS-CoV2 Omicron variants epidemic on patients with cancer in China.
Authors: Ping Xiao, Diansheng Zhong, Linlin Zhang
Journal: Journal of Clinical Oncology (2023)

e13652 Background: In December 2022, SARS-CoV2 Omicron variants were widely spread in China, and its impact on cancer patients is unclear. Methods: We retrospectively analyzed 170 cancer patients admitted to Department of Medical Oncology, Tianjin Medical University General Hospital from December 1,2022 to January 31,2023. Results: The proportion of the vaccinated population was 62% (106/170). The prevalence of Omicron variants infection was 82.35% (140/170), 86% (55/64) in unvaccinated patients and 80% (85/106) in vaccinated patients (P＞0.05). Symptoms were 77% fever (108/140), 64% cough (90/140), 35% pharyngalgia (49/140), 25% loss of taste or smell (35/140), 23% fatigue (32/140), 20% aches and pains (28/140), 19% dyspnea (27/140), 9% stuffy or runny nose (13/140) and 8% nausea or diarrhea (11/140). Among them, 48% (67/140) had 1-2 clinical symptoms; 47% (66/140) had 3-5 clinical symptoms and only 4% had more than 5 clinical symptoms. The proportion of hospitalization due to Omicron variants infection was 4%. Duration of symptoms of positive patients was 7 days (1-30)，and it was not related to vaccination status, cancer type and pulmonary disease(chronic obstructive pulmonary disease、emphysema、tuberculosis and bronchiectasis) (p＞0.05). Proportion of patients admitted to hospitalization for anti-tumor therapy at normal time (delayed 0-7 days) after Omicron variants infection was 39%（57/145）, and the hospital stay delayed 8-14 days was 20%（29/145）and 24% (35/145) more than 14 days. And it was not related to vaccination status, cancer type and pulmonary disease(chronic obstructive pulmonary disease、emphysema、tuberculosis and bronchiectasis)(p＞0.05). Conclusions: Patients with cancer had mild symptoms during Omicron variants epidemic, and the impact of Omicron on the rate of hospitalization and anti-cancer delayed treatment were relatively mild.
Neoadjuvant pyrotinib plus trastuzumab, dalpiciclib, and letrozole for triple-positive breast cancer: A pilot trial.
Authors: Jinqi Xue, Nan Niu, Shuo Wang, Guanglei Chen, Fang Qiu, Yi Zhao, Fei Xing, Xinyu Zheng, Wei Tu, Ke Li, Hai Zhao, Meiyue Tang, Qianshi Xu, Chao Liu, Yafei Zhao, Xiaofan Jiang, Shiwen Huo, Zheng Pang, Dianlong Zhang, Caigang Liu
Journal: Journal of Clinical Oncology (2023)

e12603 Background: Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib plus dalpiciclib (cyclin dependent kinase 4/6 inhibitor) and letrozole in patients with triple-positive breast cancer (TPBC), but the efficacy still needs improvement. This pilot study explored the efficacy and safety of adding trastuzumab to this neoadjuvant regimen in TPBC. Methods: Patients received five 28-day cycles of pyrotinib (320 mg once daily), dalpiciclib (125 mg once daily on days 1-21) and letrozole (2.5 mg once daily), plus six 21-day cycles of trastuzumab (8 mg/kg loading dose followed by 6 mg/kg maintenance dose on day 1), followed by surgery. The primary endpoint was tpCR (ypT0/is, ypN0) rate. Secondary endpoints were objective response rate (ORR), breast pathological complete response (bpCR; ypT0/is) rate, residual cancer burden (RCB), change in Ki-67 level from baseline to surgery, and safety. Results: Between February 16, 2022 and June 2, 2022, 12 patients were enrolled. Seven (58%; 95% CI, 27.7-84.8) patients achieved tpCR and bpCR. The rate of RCB 0-I was 75% (95% CI, 46.8-91.1%). ORR was 92% (95% CI, 64.6-98.5%). Mean Ki-67 level was significantly reduced from 45.0% (95% CI, 19.5% - 70.5%) at baseline to 17.2% (95% CI, 0.7% - 33.7%) after neoadjuvant therapy (P&lt;0.05). The most common grade 3 adverse events were diarrhea (4 [33%]) and decreased neutrophil count (3 [25%]). No grade 4 events or treatment-related deaths occurred. Conclusions: This four-drug neoadjuvant regimen shows promising pathological response in patients with TPBC, with an acceptable safety profile. The results warranted further validation. Clinical trial information: NCT05228951 .
Phase 1/2 dose expansion study evaluating first-in-class eIF4A inhibitor zotatifin in patients with ER+ metastatic breast cancer.
Authors: Ezra Rosen, Manish Sharma, David Berz, Jennifer Lee Caswell-Jin, Alexander I. Spira, Georgina A. Fulgar, Mark Densel, Nawaid Rana, Samuel Sperry, Douglas Warner, Funda Meric-Bernstam
Journal: Journal of Clinical Oncology (2023)

1080 Background: Zotatifin (eFT226) is a first-in-class, potent and sequence selective inhibitor of RNA helicase eIF4A that promotes a stable mRNA:eIF4A:drug ternary complex at specific polypurine motifs within the 5’-UTR, preventing translation of select transcripts. In preclinical models zotatifin treatment simultaneously down-regulated translation of numerous oncogenes including CDK4, ERα, ERBB2, KRAS, and CCND1. Methods: Following a 3+3 dose escalation portion of the protocol (Part 1), Part 2 is a Simon’s two-stage design of cohorts of up to 18 patients (pts) with ER+ metastatic breast cancer enrolled at the recommended phase 2 dose of zotatifin (0.07 mg/kg IV two weeks on/one week off) in combination with fulvestrant (ful) (ECBF: Expansion, Combination, Breast, Ful) or in combination with ful and abemaciclib (abema) (ECBF+A: Expansion, Combination, Breast, Ful + Abema). Key eligibility criteria included at least one line of therapy for advanced/metastatic disease, progression on hormone therapy, and in addition, the ECBF cohort required prior CDK 4/6 inhibitor (CDKI). Primary endpoint was objective response rate (ORR) per RECIST v1.1. Additional endpoints included safety, other efficacy analyses, and for Parts 1 and 2, characterization of pharmacodynamic (PD) markers and pharmacokinetics. Results: As of a data cut-off of Jan 31, 2023, 18 pts were enrolled in each cohort. Median prior metastatic lines of therapy were 3 and 7 in ECBF+A and ECBF, respectively. In 16 evaluable pts in ECBF+A cohort, there were two confirmed partial responses (PR), two additional PRs awaiting confirmatory scans, and 8 pts with best overall response (OR) of stable disease (SD). All pts with PR/unconfirmed PR received prior CDKI and ful, including one pt with disease progression on combination abema and ful as the last therapy prior to enrollment. In 18 evaluable pts in ECBF, there was one confirmed PR and six SD as best OR. There were no dose-limiting toxicities or grade (Gr) 5 adverse events (AEs) in either cohort. In ECBF+A the most common AEs (all Gr 1/2) were diarrhea (44%) and nausea (31%) and 21% of pts had Gr 3/4 AEs. The most common AEs in ECBF (all Gr 1/2) were nausea (39%) and constipation (27%), and 28% of pts had Gr 3/4 AEs. Blood-based PD markers and ctDNA in Part 1 showed dose-dependent evidence of target engagement and anti-tumor activity. Conclusions: In dose expansion cohorts of heavily pre-treated metastatic breast cancer pts, eIF4A inhibitor zotatifin showed evidence of anti-tumor activity in combination with fulvestrant and abemaciclib and had a favorable safety profile consisting of primarily grade 1/2 adverse events. Clinical trial information: NCT04092673 .
Decreased HER2 expression in residual disease following neoadjuvant therapy in patients with HER2-positive breast cancer.
Authors: Jan Paredes Mogica, Haiming Tang, Neal A. Fischbach, Haiying Zhan
Journal: Journal of Clinical Oncology (2023)

e12621 Background: Human epidermal growth factor receptor-2 (HER2) overexpression is a defining feature of roughly 20% of localized breast cancer and represents a critical target for therapy. Since the demonstration that residual disease (RD) after neo adjuvant therapy (NAT) is associated with worse prognosis and that adjuvant ado trastuzumab emtansine (tDM1) improves survival, NAT has become the standard of care for localized HER2+ breast cancer. Retesting for HER2 overexpression post resection is variable, and data is conflicting regarding the prognostic significance of changes in HER2 expression pre and post therapy. The objective of this study was to evaluate the association of pre and post neo adjuvant therapy HER2 immunohistochemistry (IHC) expression on breast cancer outcomes in our institutional database. Methods: After IRB approval, data was gathered for patients with localized HER2+ breast cancer receiving NAT including trastuzumab/pertuzumab at Yale Cancer Center between 2012 and 2022. Pathologic complete response (pCR) was defined as no residual invasive tumor in breast and lymph nodes. Patients were divided into 3 cohorts by response and HER2 IHC: Cohort 1 pCR Cohort 2 pre-treatment 3+/post treatment 1-2+, and Cohort 3 pre-treatment 3+/post treatment 3+. A Kaplan-Meier survival analysis was done to assess recurrence free survival at 36 months. Results: Within the specified time interval, we identified 104 patients with localized HER2-IHC 3+ breast cancer who received neoadjuvant therapy. The pCR rate was 62.5% (65/104), while 37.5% (39/104) of patients had RD. Among patients with RD, 58.9% (23/39) remained HER2 IHC 3+ and 41% (16/39) had decreased HER2 expression IHC1+/IHC 2+. Median follow-up was 27.9 months at time of analysis. In patients with HER2 3+ RD 26% (6/23) developed local recurrence or distant metastasis while none of patients with HER2 IHC 1+ or 2+ RD had relapse ( p= 0.0309). In patients with pCR, 6.15% (4/65) had recurrence. Kaplan-Meier survival analysis showed a significant difference between the 3 groups (log rank p= 0.004). Conclusions: In our retrospective cohort, decreased HER2 expression by IHC following neoadjuvant treatment was associated with lower recurrence rates. If confirmed, RD HER2 IHC expression could be used as a prognostic biomarker to select patients for more or less aggressive adjuvant therapy, stratify patients in adjuvant trials, and identify patients who may benefit from more intensive post therapy surveillance.
Use of tumoral LDH to predict residual tumor burden after neoadjuvant chemotherapy in breast cancer.
Authors: Soo Jung Lee, In Hee Lee, Byeongju Kang, Jee-Young Nora Park, Jeeyeon Lee, Ho Yong Park, Ji-young Park, Yee Soo Chae
Journal: Journal of Clinical Oncology (2023)

e12566 Background: The Residual Cancer Burden (RCB) score has been validated as an independent prognostic factor in all subtype of breast cancer after neoadjuvant chemotherapy (NAC). Early prediction of NAC response enable better stratification for selecting chemotherapy. Glucose metabolism in cancer cells produces various glycolytic metabolites which are related to breast cancer prognosis. In this study, we evaluated the association of glucose transporters and enzymes involved in glucose metabolism with clinic-pathological factors for early prediction of NAC response. Methods: RCB scores were retrospectively evaluated from patients with stage I-III breast cancer treated with neoadjuvant chemotherapy. We selected 7 target transporters and enzymes [GLUT1, hexokinase 2 (HK2), lactate dehydrogenase (LDH), MCT1, MCT4, IGF1RA, and IGF1RB] involved in glucose metabolism and evaluated in relationships with pretreatment clinical/pathological characteristics and treatment outcomes including RCB. Results: 236 breast cancer patients who underwent NAC followed by surgery between 2010 and 2016 in Kyungpook National University Chilgok Hospital were included. Among them, 145 (61.4%), 44 (18.6%), and 47 (19.9%) were luminal, HER2-enriched, and TNBC subtypes. RCB 0 was determined 50 (21.2%), 35 (14.8%) RCB I, 91 (38.6%) RCB II and 60 (25.4%) RCB III. After a median follow-up of 98 months, 60 (25.4%) relapses, 43 (18.2%) distant relapses, and 34 (14.4%) deaths were observed. RCB score was significantly associated with disease specific survival (DSS) and overall survival (OS). RCB III were significantly increased risk of relapse (HR=13.517, CI [1.809-101.010], P&lt;0.001). The tumoral expression rates of the target molecules were 76.0, 31.1, 42.1, 54.9, 67.9, 78.4, and 49.8% for GLUT1, HK2, LDH, MCT1, MCT4, IGF1RA, and IGF1RB, respectively. Among them, LDH was significantly associated with RCB III (OR=4.533, P=0.014) and worse disease specific survival (HR=2.29 P=0.019). Conclusions: Tumoral expression of LDH could be considered as an independent biomarker in predicting high risk of relapse (RBC III) and survival in all subtype of breast cancer.
Lipidomic signature from plasma to detect localised breast cancer.
Authors: Gillian Lamoury, Amani M. Batarseh, Cheka Kehelpannala, Dana Pascovici, Desmond Li, Kerry Heffernan
Journal: Journal of Clinical Oncology (2023)

565 Background: An effective and accurate blood test to detect localised breast cancer may increase the screening detection rate and improve patient outcomes. We have previously reported a series of lipidomic studies and derived a lipid signature from plasma enriched extracellular vesicles (EVs) that effectively distinguished people with localised breast cancer from cancer-free controls. here we report on a significant refinement to the test methodology allowing the assessment of the lipid signature directly from plasma samples and its performance, with the aim of advancing the commercial viability of the test as we move towards clinical application. Methods: Lipids were extracted from enriched EVs from plasma samples donated by fasted people with localised breast cancer and control samples (n=793) and analysed by high resolution accurate mass liquid chromatography-mass spectrometry (LC-MS). Over 400 manually curated lipids were quantified. Following variable selection, a lipid signature capable of distinguishing breast cancer samples from controls was derived. The lipid signature was modelled on each of the cohorts using leave-one-out internal cross-validation. Next, we analysed the lipids in cancer and control (n=256) plasma samples corresponding to patients from Cohorts 3 and 4 previously used for EV preparations, and applied the signature derived using EVs on plasma lipidomic data. Results: EV samples of people with breast cancer were distinguished from controls with an area under the curve (AUC) of 0.77-0.89 across 4 cohorts. When the lipid signature was assessed directly from plasma the test achieved a comparable AUC of 0.84. Assessing the markers directly from plasma samples would make the test more scalable, higher throughput and easier to perform. Conclusions: Our study demonstrated the high performance of a lipid biomarker signature derived from plasma enriched EVs for early detection of localised breast cancer. Our results suggest that that the lipidomic signature could potentially be assessed directly from plasma samples instead of EVs reducing the test complexity. Ongoing studies will optimise the plasma lipidomic signature and prospectively compare the test against mammographic and pathological diagnoses. [Table: see text]
Cancer recurrence: Detection and diagnostic intervals in Danish primary care.
Authors: Kasper Grooss, Linda Aagaard Rasmussen, Kaj Sparle Christensen, Anette Fischer Pedersen, Peter Vedsted
Journal: Journal of Clinical Oncology (2023)

e13110 Background: Danish cancer survivors receive hospital-based, specialized follow-up care with one central aim to detect cancer recurrence (CR) at an early stage. Nevertheless, CR is frequently detected outside of scheduled follow-up visits as 40-60% of CR patients encounter and present symptoms. The family physician (FP) is presumed to facilitate most of these diagnostic pathways. However, little is known about CR detection in primary care. We aim to examine diagnostic intervals, actions taken by the FP and sub-optimal events for patients presenting symptoms of CR in primary care. Methods: We are conducting a retrospective, national cohort study based on questionnaire data linked to register data at the individual level. Patients diagnosed with CR of melanoma, lung, breast, colorectal, bladder, ovarian and endometrial cancer between Jan 2022 and May 2024 are included. Patients are identified consecutively using validated, register-based algorithms. All Danish citizens have access to free healthcare and 99% are listed with a specific FP. The affiliated FP is invited to complete a questionnaire on the diagnostic pathway utilizing the patient medical record. Danish health registers provide information on the primary cancer, CR diagnosis date, comorbidity, education, sex, and age. Results: We aim to include 3,000 CR patients and expect to receive information on 1,000 CR diagnostic pathways initiated in primary care. We will present preliminary results from the first 500 responders. The proportion of diagnostic pathways initiated in primary care was 33%, hospital-based follow-up was 44%, and another route was 23%. The FPs initiated the diagnostic pathway by referral to cancer specific urgent pathway for 31% of patients, by referral to specialized private or hospital-based physician including diagnostic imaging for 30% of patients. For 31% of diagnostic pathways, the FPs reported sub-optimal or delaying events. The most frequently reported sub-optimal event was regarding clinical decisions by the FP (12%). For patients with CR of breast cancer (n=53), the mean diagnostic interval (time from first contact to CR diagnosis) was 86 days [95% CI = 61 to 112days]. Conclusions: One third of diagnostic pathways for CR was initiated in primary care. This project will provide novel, comprehensive evidence on these diagnostic pathways to inform the efforts for early detection of CR and survivorship in primary care.